Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis

Objective International guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock. Methods Systematic review and meta-analysis. We searched electronic database of MEDLINE, CENTRAL, LILACS and conference proceedings up to June 2014. We included randomized controlled trials comparing different vasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality. Other clinical and hemodynamic measurements were extracted as secondary outcomes. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) were pooled. Results Thirty-two trials (3,544 patients) were included. Compared to dopamine (866 patients, 450 events), norepinephrine (832 patients, 376 events) was associated with decreased all-cause mortality, RR 0.89 (95% CI 0.81-0.98), corresponding to an absolute risk reduction of 11% and number needed to treat of 9. Norepinephrine was associated with lower risk for major adverse events and cardiac arrhythmias compared to dopamine. No other mortality benefit was demonstrated for the comparisons of norepinephrine to epinephrine, phenylephrine and vasopressin / terlipressin. Hemodynamic data were similar between the different vasopressors, with some advantage for norepinephrine in central venous pressure, urinary output and blood lactate levels. Conclusions Evidence suggests a survival benefit, better hemodynamic profile and reduced adverse events rate for norepinephrine over dopamine. Norepinephrine should be regarded as the first line vasopressor in the treatment of septic shock.

[1]  M. Müllner,et al.  Vasopressors for hypotensive shock. , 2016, The Cochrane database of systematic reviews.

[2]  Amber E Barnato,et al.  A randomized trial of protocol-based care for early septic shock. , 2014, The New England journal of medicine.

[3]  E. Lang,et al.  Vasopressors for hypotensive shock. , 2013, Annals of emergency medicine.

[4]  J. Higgins,et al.  Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The Cochrane Collaboration , 2013 .

[5]  P. Svoboda,et al.  Terlipressin in the treatment of late phase catecholamine-resistant septic shock. , 2012, Hepato-gastroenterology.

[6]  R. Cavallazzi,et al.  Norepinephrine or Dopamine for Septic Shock , 2012, Journal of intensive care medicine.

[7]  J. Vincent,et al.  Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis* , 2012, Critical care medicine.

[8]  A. Zangrillo,et al.  Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock , 2011, Critical care.

[9]  Alok Gupta,et al.  Comparative study of dopamine and norepinephrine in the management of septic shock , 2011, Saudi journal of anaesthesia.

[10]  Michele Tarsilla Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[11]  G. Patel,et al.  EFFICACY AND SAFETY OF DOPAMINE VERSUS NOREPINEPHRINE IN THE MANAGEMENT OF SEPTIC SHOCK , 2010, Shock.

[12]  J. Vincent,et al.  Comparison of dopamine and norepinephrine in the treatment of shock. , 2010, The New England journal of medicine.

[13]  Guan Xiang-don Effect of dopamine and norepinephrine on hemodynamics and oxygen metabolism of tissue in patients with septic shock , 2010 .

[14]  Zhang Yuchu Comparison evaluation of resuscitation effect of norepinephrine and dopamine on the treatment of septic shock , 2010 .

[15]  G. Jain,et al.  Comparison of phenylephrine and norepinephrine in the management of dopamine-resistant septic shock , 2010, Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine.

[16]  M. Westphal,et al.  Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study , 2009 .

[17]  J. Parrillo,et al.  MULTICENTER STUDY OF EARLY LACTATE CLEARANCE AS A DETERMINANT OF SURVIVAL IN PATIENTS WITH PRESUMED SEPSIS , 2008, Shock.

[18]  M. Westphal,et al.  Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial , 2008, Critical care.

[19]  Therapy Study Investigators,et al.  A comparison of epinephrine and norepinephrine in critically ill patients , 2008, Intensive Care Medicine.

[20]  Sangeeta Mehta,et al.  Vasopressin versus norepinephrine infusion in patients with septic shock. , 2008, The New England journal of medicine.

[21]  S. K. Mathur,et al.  Comparison of norepinephrine and dopamine in the management of septic shock using impedance cardiography , 2007 .

[22]  D. Annane,et al.  Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial , 2007, The Lancet.

[23]  Plotkin Ll Use of vasopressin to correct hemodynamic disorders in patients with abdominal sepsis , 2007 .

[24]  L. L. Plotkin [Use of vasopressin to correct hemodynamic disorders in patients with abdominal sepsis]. , 2007, Anesteziologiia i reanimatologiia.

[25]  O. Lesur,et al.  Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial , 2006, Intensive Care Medicine.

[26]  Claude D Martin,et al.  Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study. , 2005, Critical care medicine.

[27]  I. Hozo,et al.  Estimating the mean and variance from the median, range, and the size of a sample , 2005, BMC medical research methodology.

[28]  X. Leverve,et al.  EFFECTS OF DOPAMINE AND NOREPINEPHRINE ON SYSTEMIC AND HEPATOSPLANCHNIC HEMODYNAMICS, OXYGEN EXCHANGE, AND ENERGY BALANCE IN VASOPLEGIC SEPTIC PATIENTS , 2005, Shock.

[29]  D. Annane,et al.  Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update , 2004, Critical care medicine.

[30]  Margaret M Parker,et al.  Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock , 2004, Critical care medicine.

[31]  Djillali Annane,et al.  Current epidemiology of septic shock: the CUB-Réa Network. , 2003, American journal of respiratory and critical care medicine.

[32]  D. Annane,et al.  Circulating vasopressin levels in septic shock. , 2003, Critical care medicine.

[33]  J. Vincent,et al.  Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best? , 2003, Critical care medicine.

[34]  Effects of norepinephrine, epinephrine, and norepinephrine-dobutamine on systemic and gastric mucosal oxygenation in septic shock. , 2002, Acta pharmacologica Sinica.

[35]  Y. le Tulzo,et al.  Effects of epinephrine compared with the combination of dobutamine and norepinephrine on gastric perfusion in septic shock , 2002, Clinical pharmacology and therapeutics.

[36]  D. Chittock,et al.  Beneficial Effects of Short-term Vasopressin Infusion during Severe Septic Shock , 2002, Anesthesiology.

[37]  E. Ivers,et al.  Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock , 2001 .

[38]  G. Clermont,et al.  Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care , 2001, Critical care medicine.

[39]  R. Townsend,et al.  Low-dose vasopressin in the treatment of vasodilatory septic shock. , 1999, The Journal of trauma.

[40]  E. Vicaut,et al.  Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock. , 1999, Critical care medicine.

[41]  J. Vincent,et al.  Has the mortality of septic shock changed with time. , 1998, Critical care medicine.

[42]  P. Nabet,et al.  Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study , 1997, Intensive Care Medicine.

[43]  D. Sackett,et al.  Cochrane Collaboration , 1994, BMJ.

[44]  P. Marik,et al.  The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. , 1994, JAMA.

[45]  J. Takala,et al.  Regional blood flow and oxygen transport in septic shock , 1993, Critical care medicine.

[46]  L. Papazian,et al.  Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? , 1992, Chest.

[47]  J. E. Carceller American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis , 1992, Critical care medicine.

[48]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. , 1992, Chest.

[49]  A. Groeneveld,et al.  Effect of dopamine vs norepinephrine on hemodynamics in septic shock. Emphasis on right ventricular performance. , 1989, Chest.